The proposed study is designed to elucidate some of the electrophysiological properties of smooth muscle cells from cerebral arteries. We will determine membrane electrical parameters such as; resistance, capacitance, resitivity and the degree of electrical coupling between contiguous cells. Other parameters to be measured will be; membrane potential, action potential characteristics, time constant and contractions from large conductive and small resistive arteries. The changes which occur in the above mentioned parameters in response to neurotransmitters, metabolites, altered pH and gas tensions, and platelets will be determined. We will also examine the effects of aging on the membrane electrical properties. We will look for differences in the membrane electrical properties of vessels from different brain areas since it is known that certain substances (e.g., norepinepherine) effect contraction in the arteries of certain brain areas and not others. The voltage control of contraction will be determined by simultaneously measuring membrane potential and contractions from a given arterial strip. Particular attention will be placed on determining the effects of known cerebral arterial neurotransmitters, the modulating effect of pH on the mechanisms of action of neurotransmitters, the direct effect of altered pH, and adenosine on electromechanical coupling. The ions which carry inward current during the action potential will be determined by ion substitution experiments. The voltage control over the channels which carry inward current will also be studied. The proposed studies will reveal information concerning: (1) the basic electrophsiological properties of cerebral arterial smooth muscle (2) the changes which probably occur in ion conductances responsible for the hyporeactivity to certain vasoactive agents during ageing (3) the mechanism of action of neurotransmitters, metabolites and pH, and (4) the effect of platelets and substances released from them on the membrane electrical and mechanical properties of cerebral vascular muscle.